Outcomes in patients with early-onset fetal growth restriction without fetal or genetic anomalies.

OBJECTIVE: Early-onset fetal growth restriction is associated with poor pregnancy outcomes, but frequently is due to fetal structural or chromosomal abnormalities. The objective of this study was to determine outcomes in patients with early-onset fetal growth restriction without diagnosed fetal or genetic anomalies and to identify additional risk factors for poor outcomes in these patients. METHODS: This was retrospective cohort study of singleton pregnancies in women with early-onset growth restriction defined as a sonographic estimated fetal weight <10% diagnosed between 16-28 weeks' gestation. We excluded all women with a fetal structural or chromosomal abnormality diagnosed prenatally. Data on pregnancy characteristics and outcomes were collected and analyzed for estimated fetal weight <10% and ≤5%. A nested case-control study within the cohort of patients with ongoing pregnancies was then performed to identify risk factors associated with poor pregnancy outcome using chi-squared test. RESULTS: One hundred forty-two patients were identified who met inclusion and exclusion criteria and 20 patients were found to have fetal structural or chromosomal abnormalities. In the remaining 122 patients, the incidence of intrauterine fetal demise was 5.7% and there were high rates of preterm birth <37 weeks (20%), birth weight <10% (59.3%), and gestational hypertension (14.1%). Later gestational age at diagnosis and the presence of echogenic bowel and abnormal initial umbilical artery Dopplers were associated with poor pregnancy outcome (22.56 versus 20.86 weeks, p = .046), (17.4 versus 2.2%, OR 9.68, 95%CI 1.65-56.73), and (35.3 versus 0%, OR 4.46, 95%CI 2.65-7.50) respectively. CONCLUSIONS: Patients with early-onset fetal growth restriction with no fetal structural or genetic abnormality have a high risk of poor pregnancy outcomes. Gestational age at diagnosis and certain ultrasound findings are associated with poor pregnancy outcome.

Time to Delivery after Scheduled Shirodkar Cerclage Removal in Singleton Gestations based on the Original Indication for Cerclage Placement.

OBJECTIVE: To estimate the time to delivery after elective cerclage removal and evaluate whether there is a difference based on the indication for cerclage placement. STUDY DESIGN: This was a retrospective cohort of singleton pregnancies that underwent Shirodkar cerclage placement at a single maternal-fetal medicine practice between June 2005 and June 2017. We included all scheduled elective cerclage removals >36 weeks. The primary outcome was latency to delivery. We further compared time to delivery based on the original indication for cerclage. Data were analyzed using the one-way analysis of variance and chi-square test. RESULTS: A total of 143 patients met the inclusion criteria. Of these, 40.6% were history indicated, 51.0% ultrasound indicated, and 8.4% exam indicated. The mean time from removal to delivery was 13.3 ± 8.4 days; 12.6% (18/136) of patients delivered within 24 hours of removal. When stratified by indication for cerclage, there were no significant differences for all delivery outcomes. Delaying cerclage removal to >37 weeks resulted in a statistically significantly later gestational age at delivery compared with removal between 36 and 366/7 weeks (39.0 vs. 38.3 weeks, p = 0.001). CONCLUSION: The mean time from elective Shirodkar cerclage removal to delivery is 13 days with only 12.6% of patients delivering within 24 hours of removal.

Long-term outcomes of twins based on the intended mode of delivery.

OBJECTIVE: Recent studies have shown that for twin pregnancies with a cephalic presenting first twin, planned vaginal delivery is not associated with adverse short-term neonatal outcomes, as compared to planned cesarean delivery. Our objective was to compare long-term outcomes in twins, based on planned mode of delivery. STUDY DESIGN: This was a prospective, observational cohort of twin pregnancies delivered by a single MFM practice. All the patients with a twin pregnancy >34 weeks delivered from 2005-2014 were surveyed regarding pediatric outcomes at or after 2 years of life. The survey was mail-based, with phone follow-up for nonresponses or for clarification of answers. Using chi-square, Student's t-tests, and regression analysis we compared outcomes between women who planned a vaginal (with active management of the second stage) versus cesarean delivery. The main outcome measures were: (1) a composite of major adverse outcomes (death, cerebral palsy, necrotizing enterocolitis, chronic renal, heart, or lung disease); (2) a composite of minor adverse outcomes (learning disability, speech therapy, occupational therapy, physical therapy). RESULTS: Five hundred and thirty-two women met inclusion criteria and 354 (66.5%) responded. 178 (50.3%) women planned to have a cesarean delivery (100% of whom had a cesarean delivery) and 176 (49.7%) women planned to have a vaginal delivery (83% of whom had a vaginal delivery). The average age of the children at the time of the survey was 5.9 years. There were no differences in any pediatric outcomes between the two groups. After controlling for maternal age, IVF, obesity, and preeclampsia, the planned mode of delivery was not associated with a composite of major adverse outcomes (aOR 0.673, 95% CI 0.228, 1.985), nor a composite of minor adverse outcomes (aOR 0.767, 95% CI 0.496, 1.188). CONCLUSIONS: Planned vaginal delivery with active management of the second stage of labor in twin pregnancies >34 weeks is not associated with adverse childhood outcomes.

Double versus single thrombophilias during pregnancy.

OBJECTIVE: The primary objective of this study was to evaluate whether women with double thrombophilias have a greater risk for obstetric complications as compared with women who have single thrombophilias. STUDY DESIGN: This is a retrospective cohort study of all patients in a single practice with a clinically significant inherited thrombophilia and treated with anticoagulation between 2005 and 2013. Thrombophilias evaluated include: factor V Leiden, prothrombin G20210A gene mutation, protein S deficiency, protein C deficiency, and antithrombin III deficiency. Double thrombophilia was defined as the presence of two thrombophilias or homozygosity for factor V Leiden or prothrombin Gene Mutation. Demographic and obstetrical outcome data were collected. Data on all patients with double thrombophilias who met inclusion criteria was reported. Data was then compared between the patients with double thrombophilias and single thrombophilias with singleton gestations. The data was analyzed with Pearson's chi-squared or Student's t-test as appropriate with p value <.05 used for significance. RESULTS: Eighteen patients with clinically significant double thrombophilias who met inclusion criteria were identified. Most patients delivered full term (88.9%) and appropriate for gestational age (77.8%) infants. One hundred thirty-two patients with single thrombophilias and 14 patients with double thrombophilias with singleton gestations were then compared. Demographic characteristics were not significantly different between the two groups. There were no significant differences in obstetrical outcomes between patients. CONCLUSIONS: There were no significant differences in obstetrical outcomes for patients with clinically significant double thrombophilias versus single thrombophilias when treated with anticoagulation.

The association between fetal fibronectin and spontaneous preterm birth in twin pregnancies with a shortened cervical length.

OBJECTIVE: To estimate the association between a positive fetal fibronectin (fFN) and spontaneous preterm birth (SPTB) in twin pregnancies with a shortened cervical length (CL). STUDY DESIGN: Retrospective cohort study of asymptomatic twin pregnancies managed by a single MFM practice from 2005 to 2016. We included all women with a shortened CL ≤25 mm at 22-28 weeks, and compared outcomes between women with a positive and negative fFN result. RESULTS: One hundred fifty-five patients were included, 129 (83.2%) of whom had a negative fFN and 26 (16.8%) of whom had a positive fFN. Baseline characteristics were similar between groups, except for the CL at the time of diagnosis of short cervix (15 mm in the positive fFN group versus 20 mm in the negative fFN group, p = .002). The risk of SPTB <32 weeks was significantly higher in the positive fFN group (46.2 versus 12.6%, aOR 3.54, 95% CI 1.26, 9.92) and the mean gestational age at delivery was significantly earlier (31.1 versus 35.2 weeks, p < .001). CONCLUSIONS: In asymptomatic women with twin pregnancies and a shortened CL, a positive fFN is significantly associated with SPTB and can modify the risk substantially. If performing a screening CL assessment in a twin pregnancy, fFN testing should be done concurrently.

Risk factors for blood transfusion in patients undergoing high-order Cesarean delivery.

BACKGROUND: The objective was to identify risk factors associated with blood transfusion in patients undergoing high-order Cesarean delivery (CD). STUDY DESIGN AND METHODS: This was a retrospective cohort study of patients undergoing third or more CD by a single maternal-fetal medicine practice between 2005 and 2016. We compared risk factors between women who did and did not receive a red blood cell transfusion during the operation or before discharge. Repeat analysis was performed after excluding women with placenta previa. RESULTS: A total of 514 patients were included, 18 of whom (3.5%; 95% confidence interval [CI], 2.2%-5.5%) received a blood transfusion. Placenta previa was the most significant risk factor for transfusion (61.1% of patients who received a transfusion vs. 1% of patients who did not; p < 0.001). Patients with a placenta previa had a 68.8% likelihood of requiring a blood transfusion. After women who had placenta previa were excluded, the incidence of blood transfusion was seven of 498 (1.4%; 95% CI, 0.7%-2.9%). Risk factors significantly associated with blood transfusion in the absence of previa were prophylactic anticoagulation during pregnancy and having labored. The incidence of transfusion in patients with no placenta previa, no anticoagulation, and no labor was 0.7% (95% CI, 0.3%-2.1%). Placenta previa was the most predictive risk factor for transfusion with a positive predictive value of 68.8% and a negative predictive value of 98.4%. CONCLUSION: In patients undergoing a third or more CD, only placenta previa, prophylactic anticoagulation during pregnancy, and having labored are independently associated with requiring a blood transfusion. These data can be used to guide physician ordering of prepared blood products preoperatively.

The effect of a sonographic estimated fetal weight on the risk of cesarean delivery in macrosomic and small for gestational-age infants.

OBJECTIVE: To assess the association of a sonographic estimated fetal weight (sonoEFW) with the risk of cesarean delivery in women with macrosomic or small for gestational age (SGA) infants. METHODS: Retrospective cohort of singleton deliveries >24 weeks by one MFM practice from 2005 to 2014. We included all patients who delivered an infant with macrosomia (birth weight ≥4000 g) or SGA (birth weight <10th percentile). We compared the risk of cesarean delivery between patients who did and did not have a sonoEFW within four weeks of delivery. Regression analysis was performed to control for any differences in baseline characteristics. RESULTS: In patients with macrosomic infants (n = 352), the risk of cesarean delivery was significantly higher in the sonoEFW group (45.3% versus 17.6%, aOR 2.144, 95% CI: 1.06-4.34). When we restricted the analysis to the subgroup of 265 patients who attempted vaginal delivery, our results were similar (22.3% versus 9.1%, aOR 2.73, 95% CI: 1.15-6.48). In patients with an SGA infant (n = 614), the risk of cesarean delivery was not higher in the sonoEFW group (37.4% versus 24.1%, aOR 1.23, 95% CI: 0.80-2.07), nor in those who attempted vaginal delivery (19.8% versus 13.7%, aOR 1.17, 95% CI: 0.62-2.21). CONCLUSIONS: A sonoEFW prior to delivery is independently associated with cesarean delivery in women with macrosomic infants, but not those with SGA infants. This should be considered when deciding to obtain a sonoEFW at the end of pregnancy, particularly if not for an accepted indication.

Cervical Pessary and Vaginal Progesterone in Twin Pregnancies With a Short Cervix.

OBJECTIVE: To evaluate cervical pessary as an intervention to prevent preterm birth in twin pregnancies with a short cervix. METHODS: This was a retrospective cohort study of twin pregnancies managed by a single maternal-fetal medicine practice from 2005 to 2015. We included patients at 28 weeks of gestation or less who were diagnosed with a cervical length less than 20 mm. At the time of diagnosis, all patients were prescribed vaginal progesterone. Starting in 2013, they were also offered pessary placement in addition to vaginal progesterone. We compared outcomes between patients who received a pessary and matched women in a control group in a one-to-three ratio. Women in the control group were matched to women in the case group according to cervical length and gestational age (within 5 mm and 1 week, respectively, of the case patient at the time of pessary placement). We excluded patients with cerclage, monochorionic-monoamniotic placentation, major fetal congenital anomalies discovered before or after birth, patients with twin-twin transfusion syndrome, and patients for whom there were no appropriate controls. Chi-square, Fisher exact, and Student's t tests were used, as appropriate. Regression analysis was performed to control for significant differences at baseline. RESULTS: Twenty-one patients received a cervical pessary, and they were compared with 63 matched women in the control group. As expected (as a result of matching), baseline gestational age (25.7±2.1 compared with 25.9±2.1 weeks of gestation, P=.671) and cervical length (10.9±3.6 mm compared with 11.9±4.5 mm, P=.327) were similar between the groups. Patients with a pessary had a significantly lower incidence of delivery at less than 32 weeks of gestation (1/21 [4.8%] compared with 18/63 [28.6%], adjusted P=.05), longer interval to delivery (65.2±16.8 compared with 52.1±24.3 days, adjusted P=.025), and a lower incidence of severe neonatal morbidity (2/21 [9.5%] compared with 22/63 [34.9%], adjusted P=.04). CONCLUSION: For twin pregnancies with a short cervix, the addition of a cervical pessary to vaginal progesterone is associated with prolonged pregnancy and reduced risk of adverse neonatal outcomes. A large randomized trial should be performed to verify these retrospective findings.

Fetal fibronectin, cervical length, and the risk of preterm birth in patients with an ultrasound or physical exam indicated cervical cerclage.

OBJECTIVE: The objective of this study is to estimate the risk of preterm birth in patients with an ultrasound or physical exam indicated cervical cerclage based on the results of fetal fibronectin (fFN) and cervical length (CL) screening. METHODS: Retrospective cohort of patients with a singleton pregnancy and an ultrasound or physical exam indicated Shirodkar cerclage placed by one maternal-fetal medicine practice from November 2005 to January 2015. Patients routinely underwent serial CL and fFN testing from 22 to 32 weeks. Based on ROC curve analysis, a short CL was defined as ≤15 mm. All fFN and CL results included are from after the cerclage placement. RESULTS: One hundred and four patients were included. Seventy eight (75%) patients had an ultrasound-indicated cerclage and 26 (25%) patients had a physical exam-indicated cerclage. A positive fFN was associate with preterm birth <32 weeks (15.6% versus 4.2%, p = 0.043), <35 weeks (37.5% versus 11.1%, p = 0.002), <37 weeks (65.6% versus 20.8%, p < 0.001), and earlier gestational ages at delivery (35.2 ± 3.9 versus 37.4 ± 2.9, p = 0.001). A short CL was also associated with preterm birth <35 weeks (50.0% versus 11.9%, p < 0.01), preterm birth <37 weeks (55.0% versus 29.8%, p = 0.033), and earlier gestational ages at delivery (34.8 ± 4.1 versus 37.2 ± 3.0, p = 0.004). The risk of preterm birth <32, <35, and <37 weeks increased significantly with the number of abnormal markers. CONCLUSION: In patients with an ultrasound or physical exam indicated cerclage, a positive fFN and a short CL are both associated with preterm birth. The risk of preterm birth increases with the number of abnormal biomarkers.

Optimal visualization of the fetal four-chamber and outflow tract views with transabdominal ultrasound in the morbidly obese: Are we there yet?

BACKGROUND: To compare optimal visualization of the four-chamber and outflow-tract views of the fetal heart on sonographic examination between morbidly obese (body mass index [BMI] ≥ 40 kg/m(2) ) and nonobese (BMI < 25 kg/m(2) ) pregnant women. METHODS: In this retrospective cohort study, we included records and images from 509 pregnant women who had first undergone sonographic examination between 18 and 36 weeks' fetal gestational age. RESULTS: Compared with the nonobese women, morbidly obese women had lower optimal visualization of the four-chamber and outflow-tract heart views: four-chamber view, morbidly obese, 83/186 (44.6%), versus nonobese, 283/323 (87.6%), and outflow-tract view, morbidly obese, 80/186 (43%) versus nonobese, 258/290 (89%); p < 0.0001 for each comparison. Similar outcomes were observed when the results from each subcategory of morbidly obese women (ie, BMI 40-49.9, 50-59.9, and ≥60 kg/m(2) ) were compared with that from nonobese women; p < 0.0001 for each comparison. These outcomes remained the same regardless of whether this comparison was made among those who had their examination before or at 19 weeks' or more gestational age. Among the morbidly obese women, there was no difference in optimal visualization of the four-chamber or outflow-tract views regardless of whether the examination was performed at <23 weeks' or at ≥23 weeks' gestational age: four-chamber view <23 weeks, 44.8% (78/174), versus four-chamber view ≥23 weeks, 41.7% (5/12); p = 0.8, and outflow-tract view <23 weeks, 43.1% (75/174), versus outflow-tract view ≥23 weeks, 41.7% (5/12); p = 0.9. After controlling for maternal age and race, the odds of visualizing the four-chamber and outflow-tract views in the morbidly obese were reduced compared with those in their nonobese counterparts: odds ratio (OR) for four-chamber, 0.13; 95% confidence interval (CI), 0.08-0.21, and OR for outflow-tract, 0.11; 95% CI, 0.07-0.17. CONCLUSIONS: Optimal visualization of the fetal four-chamber and outflow-tract views was achieved in less than 50% of morbidly obese women, compared with almost 90% in nonobese women.

Asymptomatic "placental prolapse" with cervical funneling in a patient with complete placenta previa.

We describe the transvaginal sonographic findings in a patient with complete placenta previa and increased risk of preterm birth owing to a prior history of mid-trimester pregnancy loss in whom we observed a short cervix and prolapse of the placenta and fetal membranes into the endocervical canal. We believe that this could lead to antepartum hemorrhage and mandate close observation when diagnosed. We introduced the term "placental prolapse" to describe our finding.

Infection and smoking are associated with decreased plasma concentration of the anti-aging protein, α-klotho.

OBJECTIVE: The objective of this study was to determine whether maternal plasma concentrations of soluble α-klotho are different between women with microbial invasion of the intra-amniotic cavity (MIAC) and those without MIAC among preterm labor and intact membranes (PTL) or preterm prelabor rupture of membranes (pPROM). METHODS: A cross-sectional study was conducted to include women in the following groups: i) PTL with MIAC (n=14); ii) PTL without MIAC (n=79); iii) pPROM with MIAC (n=30); and iv) pPROM without MIAC (n=33). MIAC was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Amniotic fluid samples were obtained within 48 h of maternal blood collection. Plasma concentration of soluble α-klotho was determined by ELISA. RESULTS: i) The median plasma concentration (pg/mL) of soluble α-klotho was significantly lower in patients with MIAC than in those without MIAC (787.0 vs. 1117.8; P<0.001). ii) Among patients with PTL, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (787.0 vs. 1138.9; P=0.007). iii) Among patients with pPROM, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (766.4 vs. 1001.6; P=0.045). iv) There was no significant difference in the median plasma concentration of soluble α-klotho between PPROM without MIAC and PTL without MIAC (1001.6 pg/mL vs. 1138.9 pg/mL, respectively; P=0.5). v) After adjustment for potential confounders (maternal age, tobacco use, gestational age at venipuncture), soluble α-klotho remained significantly associated with MIAC (P=0.02); and vi) Among patients without MIAC, smoking was significantly associated with a lower median plasma concentration soluble α-klotho than in non-smokers (794.2 pg/mL vs. 1382.0 pg/mL, respectively; P<0.001); however, this difference was not observed in patients with MIAC. CONCLUSIONS: Intra-amniotic infection occurring at preterm gestations (regardless of membrane status) was associated with a decrease in maternal plasma concentrations of soluble α-klotho. Moreover, among patients without infection, the plasma concentration of α-klotho was lower in smokers.